Desmogleins are a family of proteins that function as a biological adhesive, holding cells together in tissues that experience frequent mechanical stress. They are part of a larger class of proteins called cadherins, which are fundamental for cell-to-cell adhesion. Desmogleins act as molecular rivets that secure cells to one another, ensuring the structural integrity of tissues like the skin and the heart.
Their primary role is to maintain the cohesion of tissues that must withstand force, preventing them from tearing or separating. This function is especially apparent in the outer layer of the skin, which is constantly subjected to stretching and friction.
The Cellular Glue Function
Desmogleins perform their adhesive function as a component of intercellular junctions called desmosomes. These structures act as strong anchoring points, linking adjacent cells. The desmoglein proteins extend from the inside of one cell, cross the cell membrane, and link up with desmogleins from a neighboring cell in the space between them.
This external connection is only one part of the system. Inside the cell, desmogleins are linked to the internal scaffolding, known as the cytoskeleton. In skin cells, they connect to a network of tough filaments made of a protein called keratin. This internal linkage distributes mechanical stress across the entire tissue, providing resilience and preventing structural failure.
This arrangement is particularly dense in tissues that endure constant physical force, such as the epidermis (the outermost layer of the skin) and the myocardium (the muscle tissue of the heart). In the epidermis, this system ensures the skin remains an effective barrier, while in the heart, it maintains the integrity of the muscle as it contracts.
Types of Desmogleins and Their Locations
The desmoglein family consists of four main types, and their specific locations within the body are closely tied to their functions. The distribution of these proteins is not uniform, which is a factor in how certain diseases manifest.
- Desmoglein 1 (Dsg1) is predominantly found in the superficial, or upper, layers of the epidermis. It holds the outermost skin cells together, forming the barrier that protects the body from the environment.
- Desmoglein 3 (Dsg3) is located in the deeper, or basal, layers of the epidermis. It is also highly expressed in mucous membranes, such as the lining of the mouth and throat, where it is responsible for cell adhesion.
- Desmoglein 2 (Dsg2) is the most widely distributed type. While present in the basal layers of the skin, its most notable location is in heart muscle cells (cardiomyocytes). Dsg2 is also found in the lining of the intestine.
- Desmoglein 4 (Dsg4) has a more specialized role and is primarily associated with hair follicles. It contributes to the structural integrity of the hair shaft and the proper anchoring of hair.
Role in Autoimmune Skin Diseases
In certain autoimmune diseases, the body’s immune system mistakenly identifies desmogleins as foreign and produces antibodies against them. These autoantibodies disrupt the adhesive function of the desmogleins, breaking the bonds between cells. This process, known as acantholysis, leads to the formation of blisters and erosions as the cells separate.
Pemphigus vulgaris is an autoimmune condition linked to antibodies targeting Desmoglein 3 (Dsg3). Because Dsg3 is abundant in mucous membranes, the disease often begins with painful sores inside the mouth. In many cases, the immune system also produces antibodies against Desmoglein 1 (Dsg1), leading to flaccid, deep blisters on the skin.
A related condition, pemphigus foliaceus, is caused by antibodies that specifically target Desmoglein 1 (Dsg1). Since Dsg1 is concentrated in the superficial layers of the epidermis, this disease is characterized by superficial, crusty blisters on the skin. Mucous membranes are not affected because of the low expression of Dsg1 in those tissues.
Connection to Genetic and Cardiac Conditions
Desmoglein-related diseases can also arise from genetic mutations in the genes that provide the instructions for making these proteins. These inherited disorders are caused by faulty gene coding, not an immune system attack.
Arrhythmogenic Cardiomyopathy (ACM) is a heart condition that can cause life-threatening irregular heartbeats. Many cases of ACM are linked to mutations in the gene for Desmoglein-2 (DSG2). When the DSG2 gene is mutated, the resulting faulty Dsg2 protein compromises adhesion between heart muscle cells. This weakness can lead to the progressive replacement of healthy muscle tissue with scar tissue and fat, impairing the heart’s function.
Genetic defects in desmogleins can also cause skin disorders. Striate Palmoplantar Keratoderma (SPPK) is a condition characterized by thick, hardened skin on the palms and soles, often in a linear pattern. This disorder can be caused by mutations in the gene for Desmoglein 1 (DSG1).